62856-00-2

Upstream product

• 103-82-2 phenylacetic acid 
• 78-81-9 isobutylamine 
• 103-81-1 Benzeneacetamide 
• 5330-97-2 N-hydroxy-2-phenylacetamide 
• 100389-67-1 N-(2-methylprop-1-enyl)-2-phenylacetamide 
• 103-80-0 phenylacetyl chloride 

Relevant academic research and scientific papers

Catalytic chemical amide synthesis at room temperature: One more step toward peptide synthesis

An efficient method has been developed for direct amide bond synthesis between carboxylic acids and amines via (2-(thiophen-2-ylmethyl)phenyl)boronic acid as a highly active bench-stable catalyst. This catalyst was found to be very effective at room temperature for a large range of substrates with slightly higher temperatures required for challenging ones. This methodology can be applied to aliphatic, α-hydroxyl, aromatic, and heteroaromatic acids as well as primary, secondary, heterocyclic, and even functionalized amines. Notably, N-Boc-protected amino acids were successfully coupled in good yields with very little racemization. An example of catalytic dipeptide synthesis is reported.

Direct amidation of carboxylic acids catalyzed by ortho-iodo arylboronic acids: Catalyst optimization, scope, and preliminary mechanistic study supporting a peculiar halogen acceleration effect

The importance of amides as a component of biomolecules and synthetic products motivates the development of catalytic, direct amidation methods employing free carboxylic acids and amines that circumvent the need for stoichiometric activation or coupling reagents. ortho-Iodophenylboronic acid 4a has recently been shown to catalyze direct amidation reactions at room temperature in the presence of 4A molecular sieves as dehydrating agent. Herein, the arene core of ortho-iodoarylboronic acid catalysts has been optimized with regards to the electronic effects of ring substitution. Contrary to the expectation, it was found that electron-donating substituents are preferable, in particular, an alkoxy substituent positioned para to the iodide. The optimal new catalyst, 5-methoxy-2-iodophenylboronic acid (MIBA, 4f), was demonstrated to be kinetically more active than the parent des-methoxy catalyst 4a, providing higher yields of amide products in shorter reaction times under mild conditions at ambient temperature. Catalyst 4f is recyclable and promotes the formation of amides from aliphatic carboxylic acids and amines, and from heteroaromatic carboxylic acids and other functionalized substrates containing moieties like a free phenol, indole and pyridine. Mechanistic studies demonstrated the essential role of molecular sieves in this complex amidation process. The effect of substrate stoichiometry, concentration, and measurement of the catalyst order led to a possible catalytic cycle based on the presumed formation of an acylborate intermediate. The need for an electronically enriched ortho-iodo substituent in catalyst 4f supports a recent theoretical study (Marcelli, T. Angew. Chem. Int. Ed.2010, 49, 6840-6843) with a purported role for the iodide as a hydrogen-bond acceptor in the orthoaminal transition state.

Direct amidation of carboxylic acids catalyzed by ortho-iodo arylboronic acids: Catalyst optimization, scope, and preliminary mechanistic study supporting a peculiar halogen acceleration effect

The importance of amides as a component of biomolecules and synthetic products motivates the development of catalytic, direct amidation methods employing free carboxylic acids and amines that circumvent the need for stoichiometric activation or coupling reagents. ortho-Iodophenylboronic acid 4a has recently been shown to catalyze direct amidation reactions at room temperature in the presence of 4A molecular sieves as dehydrating agent. Herein, the arene core of ortho-iodoarylboronic acid catalysts has been optimized with regards to the electronic effects of ring substitution. Contrary to the expectation, it was found that electron-donating substituents are preferable, in particular, an alkoxy substituent positioned para to the iodide. The optimal new catalyst, 5-methoxy-2-iodophenylboronic acid (MIBA, 4f), was demonstrated to be kinetically more active than the parent des-methoxy catalyst 4a, providing higher yields of amide products in shorter reaction times under mild conditions at ambient temperature. Catalyst 4f is recyclable and promotes the formation of amides from aliphatic carboxylic acids and amines, and from heteroaromatic carboxylic acids and other functionalized substrates containing moieties like a free phenol, indole and pyridine. Mechanistic studies demonstrated the essential role of molecular sieves in this complex amidation process. The effect of substrate stoichiometry, concentration, and measurement of the catalyst order led to a possible catalytic cycle based on the presumed formation of an acylborate intermediate. The need for an electronically enriched ortho-iodo substituent in catalyst 4f supports a recent theoretical study (Marcelli, T. Angew. Chem. Int. Ed.2010, 49, 6840-6843) with a purported role for the iodide as a hydrogen-bond acceptor in the orthoaminal transition state.

Titanium(IV) isopropoxide as an efficient catalyst for direct amidation of nonactivated carboxylic acids

Secondary and tertiary amides are formed in high yields, in an efficient and environmentally benign titanium(IV) isopropoxide catalyzed direct amidation of carboxylic acids with primary and secondary amines. Georg Thieme Verlag Stuttgart ? New York.

BORONIC ACID CATALYSTS AND METHODS OF USE THEREOF FOR ACTIVATION AND TRANSFORMATION OF CARBOXYLIC ACIDS

The present application provides methods and catalysts for activation of carboxylic acids for organic reactions. In particular, methods are disclosed for direct nucleophilic addition reactions, such as, amidation reactions with amines, cycloadditions, and conjugate additions, using boronic acid catalysts of formula I, II or III: Also included are novel boronic acid catalysts of formula IV, V and III:

Reactions of acyl nitroso compounds with amines: Production of nitroxyl (HNO) with the preparation of amides

Oxidation of hydroxamic acids in the presence of amines generates nitrous oxide (N2O) and the corresponding amide. The identification of N2O suggests the intermediacy of nitroxyl (HNO). Retro-Diels Alder dissociation of cyclopentadiene-acyl nitroso compound cycloadducts releases N2O with amide formation.

Rapid Acid-catalysed and Uncatalysed Hydration of Ketenimines

The rates of hydration of a series of ketenimines (9) have been examined in water (μ 1.0; 25 deg) over the pH range 2-13.Three mechanisms of hydration to the amides (8) were noted: (a) general acid catalysis by proton transfer from H3O(1+) in the pH range 2-7 (giving kH3O(1+)/kD3O(1+) 2.65); (b) general acid catalysis by H2O at pH > 7 (where kH2O/kD2O = 4.8); (c) rate determining HO(1-) attack.The last mechanism was only shown by N-arylketenimines, e.g. (9e); other N-alkylketenimines continue to react by rate-determining proton transfer from water even at pH 13.This result is confirmed by the incorporation of just one deuterium when (9a) reacted in acidic or basic D2O, while the deuteriated ketenimine (9f) does not loose the label on the reaction in water.Substituent effects are parallel for reactions involving H(1+) transfer from H3O(1+) or H2O; the major effects are obtained on changing substituents at carbon (the protonation site).For example, replacement of C-H by C-Me reduces the reactivity by 10-20-fold, while replacement of C-Me by C-Ph reduces the rate of hydration by >100-fold.Ammonium ions also generally react with ketenimines by rate-determining H(1+) transfer to the ketenimine followed by trapping of the nitrilium ion formed by the free amine.Only with the strongest amine base studied (piperidine) does direct nucleophilic attack on the ketenimine compete.